The continuous introduction into technical use of new materials which cannot be radiation or heat sterilized or sterilized by exposure to liquid systems has necessitated the development of other means of sterilization. A major modern method for this purpose is based on the use of gaseous chemical agents. Such chemical compounds must be employed selectively, however, as only those which kill spores can be classified as chemical sterilizing agents. A wide variety of antimicrobial agents is available, but in most instances they do not kill resistant bacterial spores. Microbiocides are specifically limited to the destruction of the type of organism suffixed by "cide", e.g., bactericide refers to killing of bacteria, fungicide to fungi, viricide to viruses and sporicide to spores, both bacterial and fungal. Since bacterial spores are the most difficult to destroy, only sporicides may be considered synonymous with chemosterilizers. These may be defined as chemical agents which, when utilized properly, can destroy all forms of microbiological life, including bacterial and fungal spores and viruses.
Gaseous ethylene oxide and formaldehyde are used at many hospitals and medical research facilities to sterilize equipment or work areas that cannot be readily heat- or liquid-sterilized. Formaldehyde, if applied in high concentrations, is likely to leave a residue of solid paraformaldehyde. For this reason, it is often avoided in the sterilization of delicate equipment or in situations in which allergic reactions to this substance may occur. Ethylene oxide, which, unlike formaldehyde, penetrates well into porous materials, is strongly absorbed by rubber and by many plastics so that the vapors are not readily eliminated by brief aeration.
The publication of research relating to the mutagenicity and oncogenicity of both ethylene oxide and formaldehyde threatens to lead to severe limitations, if not outright bans, on the use of these compounds as sterilizing agents. The limitations would significantly increase the costs associated with ethylene oxide sterilization.
Apart from its potential health hazards, ethylene oxide is difficult to handle at the concentrations and temperatures required for effective sterilization. Ethylene oxide at a 3-80 percent concentration in air is violently explosive and so ethylene oxide is commonly employed in admixture with an inert gas such as a fluorocarbon, for example, 12 percent ethylene oxide and 88 percent Freon 12.RTM. (E. I. DuPont Co.). In the sterilization of medical products, temperatures as high as 130.degree.-140.degree. F. are commonly employed to ensure sterility at chamber concentrations of 300-1200 mg/l of ethylene oxide. Prehumidification followed by gas exposure times of at least 4.0 hours are commonly employed. Also, ethylene oxide is more effective in killing dry spores on porous materials, such as paper or fabrics, than on nonporous materials such as glass, ceramics, hard plastics and metals. See C. W. Bruch and M. K. Bruch, Gaseous Disinfection, in Disinfection, M. A. Benarde, Ed., Marcel Decker, Pub., New York (1970) at pages 149-207.
Chlorine dioxide has long been recognized as being biologically active and early studies indicated that it possesses bactericidal, viricidal and sporicidal properties when applied in aqueous solution at minimum concentrations of about 0.20-0.25 mg/l. See W. J. Masschelein in Chlorine Dioxide: Chemistry and Environmental Impact of Oxychlorine Compounds, R. C. Rice, ed., Ann Arbor Science Pub. (1979); G. M. Ridenour, et al., Water & Sewage Works, 96, 279 (1949). However, more recent patents have stated that aqueous chlorine dioxide alone is not sporicidal unless used in the presence of stabilizers. See Snyder, U.S. Pat. No. 4,073,888. Sterilization with aqueous chlorine dioxide suffers from all of the general disadvantages associated with the use of aqueous sterilizing agents, including formulation and handling difficulties, the inability to sterilize moisture-sensitive equipment or substances, and the deposition of residues upon drying.
Little is known of the gas-phase chemistry of chlorine dioxide in air. At concentrations above about 10% (i.e., at about 288 mg per liter), the compound is unstable and sometimes detonates--probably in a shock or light-catalyzed decomposition. For this reason, chlorine dioxide gas cannot be stored. At the same concentration in aqueous solution, it is quite stable.
The chemistry of chlorine dioxide in water is thought to be influenced by the formation of hydrates. At low temperatures (but above 0.degree. C.), high concentrations of chlorine dioxide precipitate out as hydrates of somewhat variable composition; warming permits these to redissolve. It is likely that chlorine dioxide in these warmed solutions still has some water molecules clustered about it. Such hydrates would not, of course, occur in the vapor phase.
In general, both the distance of molecules from one another in the gas phase and the absence of polar solvent effects must profoundly alter the chemistry of chlorine dioxide in air. Finally, only relatively small molecules have sufficient vapor pressure to co-exist with chlorine dioxide. Thus, compounds frequently available for reaction in natural water (e.g., proteins, certain amino acids, humic acids and fulvic acids) would not be found in the vapor state.
Lovely (U.S. Pat. No. 3,591,515) discloses powdered compositions which may be formulated to release 10-10,000 ppm of chlorine dioxide gas. The liberated chlorine dioxide gas is disclosed to be useful to kill bacteria and prevent fungus growth on fruit during shipment.
Due to the handling difficulties associated with chlorine dioxide, the differences in its gas phase and solution chemistry, and the inconsistencies in the above-cited work, chlorine dioxide gas has not been demonstrated to possess utility as a chemosterilizing agent at any concentration.
Accordingly, it is an object of the present invention to utilize chlorine dioxide gas as a chemosterilizing agent, i.e., as a sporicide, for a variety of materials commonly used for medical and dental implements and products.
It is another object of the present invention to utilize chlorine dioxide gas as a chemosterilizer at short exposure times and at ambient temperatures, pressures and relative humidities.
It is another object of the present invention to utilize chlorine dioxide as a chemosterilizing agent for materials such as medical implements which are sealed within gas permeable wrappings.
It is a primary object of the present invention to utilize chlorine dioxide gas as a chemosterilizer for impermeable surfaces, which may be dried prior to sterilization.
Other objects, advantages and novel features of the present invention will be apparent to those skilled in the art from the following description and appended claims.